NM_001013579.3:c.547G>C

Variant names:

• chrX-70238298-G-C
• NM_001013579.3:c.547G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001013579.3(AWAT1):​c.547G>C​(p.Gly183Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: AWAT1 NM_001013579.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.72

Genes affected

AWAT1 (HGNC:23252): (acyl-CoA wax alcohol acyltransferase 1) The protein encoded by this gene belongs to the diacylglycerol acyltransferase family. It esterifies long chain (wax) alcohols with acyl-CoA-derived fatty acids to produce wax esters. Wax esters are enriched in sebum, suggesting that this enzyme plays a central role in lipid metabolism in skin. Consistent with this observation, this protein is predominantly expressed in the sebaceous gland of the skin. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AWAT1	NM_001013579.3	c.547G>C	p.Gly183Arg	missense_variant	Exon 5 of 7	ENST00000374521.4	NP_001013597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AWAT1	ENST00000374521.4	c.547G>C	p.Gly183Arg	missense_variant	Exon 5 of 7	1	NM_001013579.3	ENSP00000363645.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 12, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.547G>C (p.G183R) alteration is located in exon 5 (coding exon 5) of the AWAT1 gene. This alteration results from a G to C substitution at nucleotide position 547, causing the glycine (G) at amino acid position 183 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.052	T
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.045	N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.084
Sift	Benign	0.043	D
Sift4G	Benign	0.23	T
Polyphen		0.82	P
Vest4		0.46
MutPred		0.34		Gain of stability (P = 0.0197);
MVP		0.96
MPC		0.72
ClinPred		0.84	D
GERP RS		4.1
Varity_R		0.30
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-69458148;